Micro-adsorption detector and method of using same

ABSTRACT

A microadsorption detector is disclosed having at least three adsorption-heat-detection cells serially disposed in close proximity to each other along the flow path for a fluid stream in which constituents are to detected. The third adsorption-heatdetection cell permits the electrical outputs of the cells to be combined in at least two pairs to form at least two separate composite output signals. The composite signals each comprise a combination of the outputs of at least two cells. Use of different adsorptive fill materials in the pairs of cells yields qualitative information concerning the constituents to be detected in the fluid stream. At least one of the cells would normally be filled with a relatively inert, nonadsorptive material and serve as a reference cell to compensate for extaneous temperature changes common to all the cells. Four or more cells can be arranged to compensate for flow sensitivity. The signal from one pair of cells, both members of which are filled with the same type of adsorptive material, will compensate that part of the signal from other pairs of cells which is due to change in flow rate.

United States Patent [72] Inventor Miner Nelson Munk Walnut Creek,Calif. [21] Appl No 793,948 [22} Filed Jan. 27, 1969 [45] Patented July13, I971 [73] Assignee Varian Associates Palo Alto, Calif.

(54] MICRO-ABSORPTION DETECTOR AND METHOD OF USING SAME 7 Claims, 12Drawing Figs.

[52] U.S.Cl 73/23.1, 73/61.1C, 23/254 [51] Int. Cl ..G0ln 31/08, GOln11/00 [50] Field Search 73/23.l, 61.1 LC,25,26,27,29

[56] Relerences Cited UNITED STATES PATENTS 2,596,992 5/1952 Fleming73/27 2,633,737 4/1953 Richardson 73/27 2,868,011 1/1959 Coggeshali...73/23.l 3,263,488 8/1966 Martin 73/23.l 3,408,854 11/1968 Larson 73/23.1

OTHER REFERENCES Hupe et al., A Micro Adsorption Detector for GeneralUse in Liquid Chromatography." appearing in JOURNAL OF GAS CHROMATOGRAPHApril 1967. page 197 etseq Paynes, Gas Analysis by Measurement ofThermal Conductivity, pages 87 and 165 dated Feb. 1948 Library #QD 121D3 Primary Examiner-Richard C Queisser Assistant Examiner- Ellis J. KochAttorneys-William J. Nolan and Leon F. Herbert ABSTRACT: Amicroadsorption detector is disclosed having at least threeadsorption-heat-detection cells serially disposed in closeproximity toeach other along the flow path for a fluid stream in which constituentsare to detected. The third adsorption-heat-detection cell permits theelectrical outputs of the cells to be combined in at least two pairs toform at least two separate composite output signals. The compositesignals each comprise a combination of the outputs of at least twocells. Use of different adsorptive fill materials in the pairs of cellsyields qualitative information concerning the constituents to bedetected in the fluid stream. At least one of the cells would normallybe filled with a relatively inert, nonadsorptive material and serve as areference cell to compensate for extaneous temperature changes common toall the cells. Four or more cells can be arranged to compensate for flowsensitivity. The signal from one pair of cells, both members of whichare filled with the same type of adsorptive material, will compensatethat part of the signal from other pairs of cells which is due to changein flow rate.

PATENTEU JUL 1 3191: 3,592,043

SHEET 1 [IF 2 LIQUID CHROMATOGRAPHIC SAMPLE COMPARATOR? 7 2 FIG. 7 i725\ RI INVENTOR.

MINER N.HUNK FIG.6 lfljli z BY M yea RNEY MICRO-ABSORPTION DETECTOR ANDMETHOD OF USING SAME DESCRIPTION OF THE PRIOR ART Heretofore,microadsorption detector cells have been serially arranged in the flowpath of the output of a liquid chromatographic column for detecting theoutput peaks. Such a detector is described in the Journal of GasChromatography, page 197, Apr. 1967. While such a detector has numerousadvantages for use in liquid chromatography (LC), it has onedisadvantage. This disadvantage is that the detector is relativelysensitive to changes in fluid flow rate. This flow sensitivity precludesthe use of the detector with pulsating type pumps and translates a longterm change in fluid flow rate into an annoying base line drift. Thereason for the flow sensitivity is that the heat dissipated in theupstream thermistor is carried downstream to the second thermistor. Theamount of heat carried to the downstream thermistor is a function of theflow rate.

Therefore, it is desirable to provide a microadsorption detector theoutput of which is relatively independent of the flow rate such that thedetector may be used with conventional pulsating pumps. It is alsodesired that the microadsorption detector be made more specific and morequalitative as regards the detection of certain sample constituents.

SUMMARY OF THE PRESENT INVENTION The principal object of the presentinvention is the provision of an improved microadsorption detectoruseful, for example, as a detector for L.C. and for analyzing certainsamplesolvent-adsorbent systems.

One feature of the present invention is the provision of at least threeadsorption detector cells serially disposed along the flow path of afluid stream, whereby the individual outputs of each of the detectorcells may be combined in at least two pairs to form at least twoseparate composite output signals, such composite signals eachcomprising a combination of the outputsof at least two cells, thuspermitting comparison of the output signals to obtain improved detectionof certain constituents of the fluid stream.

Another feature of the present invention is the same as the precedingfeature wherein there are at least four of the adsorption detectioncells serially disposed along the stream.

Another feature of the present invention is the same as any one or moreof the preceding features wherein one pair of adsorption cells includesa different active adsorptive packing material than the other pair ofcells, whereby comparison of the output signals yields qualitativeinformation concerning the adsorptive characteristics of the sampleunder analysis.

Another feature of the present invention is the same as the first andsecond features wherein one of the pairs of detector cells includes arelatively active adsorptive fill material, whereas the second pair ofdetector cells includes an inactive or inert fill material, if any, andwherein the output of the second pair of detector cells is subtractedfrom the output of the first pair of detector cells to decrease thesensitivity of the overall detector to fluid flow rate, whereby thedetector may be utilized with pulsating type pumps.

Another feature of the present invention is the same as one or more ofthe preceding features including the adsorptive detector cells incombination with a liquid chromatographic column such that the detectorcells are disposed to detect constituents in the effluent liquid streamof the column.

Other features and advantages of the present invention will becomeapparent upon a perusal of the following specification taken inconnection with the accompanying drawings wherein:

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic line diagram,partly in block diagram form, of a chromatograph employing features ofthe present invention,

FIG. 2 is a schematic circuit diagram of a prior art microadsorptiondetector,

FIG. 3 is a schematic circuit diagram of a microadsorption detectorincorporating features of the present invention,

FIG. 4 is a schematic block diagram of a comparator employed forcomparing the outputs ofthe circuit of FIG. 3,

FIG. 5 is a schematic drawing, partly in block diagram form, of arecorder for comparing the outputs of the circuit of FIG. 3,

FIG. 6 is a schematic diagram of an alternative embodiment of thedetector of the present invention,

FIG. 7 is a schematic circuit diagram of a microadsorptive detectorincorporating features of the present invention,

FIG. 8 is a plot of detected output signal amplitude versus flow ratefor an empty detector and for a packed detector and for empty detectorsat two different levels of bridge voltage,

FIG. 9 is a circuit similar to that of FIG. 7 depicting an alternativeembodiment of the present invention for eliminating flow sensitivity,

FIG. 10 is a schematic block diagram of a circuit for com paring theoutputs of the circuit of FIG. 9,

FIG. 11 is a schematic circuit diagram for an alternative detectorcircuit to that of FIG. 9, and

FIG. 12 is a longitudinal sectional view ofa microadsorptive detectorincorporating features of the present invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS Referring now to FIG. 1, thereis shown a microadsorption detector 1 incorporating features of thepresent invention. The adsorption detector includes 3 detector cells 8,,S and R serially arranged in close proximity to each other along theflow path of a fluid stream 2. The fluid stream may either be a gas or aliquid. In a preferred embodiment the adsorption detector l is employedfor analyzing the effluent stream of a liquid chromatographic column 3into which a sample to be analyzed is injected, as indicated at 4. Theoutput of the chromatographic column 3 comprises a time separation ofsample constituents in a solvent stream. As the sample stream 2 passesthrough the detector 1 the sample peaks are sequentially adsorbed andsometimes desorbed from the packing material 5, if any, positionedwithin each of the detector cells 8,, S5 and R. The adsorptive fillmaterial 5 is held within each of the cells by means of suitable fluidpermeable walls such as filter paper membranes 6.

The microadsorption detector 1 makes use of the same physical effectwhich is used in separation by elution chromatograph, i.e., thedifferent affinities of the eluent and the eluted substance for thestationary phase. Thus, the method is equally valid when the eluent isgaseous or liquid, the stationary phase solid or liquid. With eachsequential step of adsorption and desorption in the various cells of thedetector 1, there is associated both an evolution and an uptake of heatwhose values are of equal but of opposite sign. The heats of adsorptionand desorption are proportional to the concentration of the substance inthe stationary phase. A change in the concentration of the substance inthe eluent will, therefore, cause a change of temperature, provided theeluted substance and the eluent have differing affinities for thestationary phase. Thus, there is a rise in temperature in each of thecells when the maximum of a peak in the output of the chromatographiccolumn reaches the particular cell. The following fall in temperaturewould generally be equal to the preceding rise in temperature, exceptthat there is an exchange of heat with the immediate surroundings.Therefore, as the front of a peak passes a given point, a certain amountof the heat evolved will be transported away so that the temperatureexpected under adiabatic conditions will not be reached. On the passageof the end of the peak this heat dissipates and the temperature willsink below the ideal starting temperature. The original temperature willonce again be obtained by conduction from the surroundings. Typicalchanges in temperature are as shown by the signal traces of FIG. 5.

Each of the detector cells 8,, S and R includes a thermistor sensingelement 7 for sensing the change in temperature of the cell withadsorption and desorption. The prior art electrical circuit forconnection of the thermistors of the sample S, and reference cells R,respectively, is shown in FIG. 2. Briefly, the thermistor of the samplecell S, and the thermistor of the reference cell R were connected infirst and second arms, respectively, on the same side of a wheatstonebridge l2. Reference resistors 13 and 14 were connected in the remainingtwo arms of the bridge, on the opposite side thereof, for balancing thebridge, in the absence ofa signal to be detected. The reference cell wasfilled with an inert packing material 5 such as glass beads, whereas thereference cell S, was filled with a relatively active adsorptivematerial.

The bridge was energized from a constant voltage supply 15 and thechanges of temperature of the sensing cell 8,, relative to the referencecell R, were sensed by thermistors 7 and resulted in an unbalance of thebridge, producing an electrical output signal E The output signal hadthe characteristic shape as shown by either of the signal tracesdepicted in FIG. 5.

The problem with this prior art arrangement is that it yieldsquantitative information but very little qualitative information. Oftentimes the output signal would have a plurality of relatively closelyspaced peaks and it would be desirable to differentiate the differentsample constituents within the one composite peak.

Therefore, the adsorption detector 1, of the present invention, wasconstructed to include a second sensing cell S, cmploying a differentadsorptive fill material than that employed in the first sensing cellS,. It is quite unlikely that two different sample constituents willhave the same adsorptive characteristics for two different adsorptivematerials, especially when the materials are selected to providedifferent adsorptive characteristics; for example, one of the adsorptivefill materials could be an ion exchange resin, whereas the otheradsorptive material in the second sensing cell could be a surfaceadsorptive material. Alternatively, a polar surface adsorptive fillmaterial may be used in one cell and a nonpolar surface adsorptivematerial used in the second cell. A comparison of the adsorptivecharacteristics of the sample on the two different adsorptive materialswill yield qualitative results not obtainable by use ofa singleadsorptive fill material.

Referring now to FIG. 3, there is shown a bridge network for use withthe adsorptive detector ll of FIG. 1. The circuit is essentially thesame as that of FIG. 2 with the exception that it includes a secondbridge network 16 connected in parallel with the first bridge 12. Thesecond bridge network 16 includes the thermistor 7 of the second sensingcel 5: connected in one side of the wheatstone bridge 16 with thethermistor 7 of the reference cell R. The other side of the wheatstonebridge 16 includes balancing resistors 13' and 14'. The output signal Eof the second bridge 16 is taken across the diagonal thereof, in theconventional manner.

A switching network 117 is provided for sequentially switching thethermistor 7 of the reference cell R into circuit in alternate ones ofthe bridges l2 and 16, at a relatively rapid rate. Although mechanicallyganged switches 18 are shown, for the sake ofexplanation, it is to beunderstood that any conventional switching arrangement may be employed,such as commutators, gating diodes, and the like, in place of themechanical switches 18. Also, a stage of synchronous detectionreferenced to the switching rate is preferably employed for detectingthe output signals of the bridges l2 and 16 such that the pulsatingeffect of the switching on the output signals E, and E, can beeliminated. The synchronously detected output signals [5,, E, are thenfed to a comparator 19 as shown in FIG. 4. The output of the comparatoris an output signal determinative of the difference between the twooutput signals E, and E Alternatively, the two synchronously detectedoutput signals E, and E, may be fed to galvanometer recorders 21 and 22for recording their respective output signals on the same time scale ona strip chart recorder for visual comparison.

Comparison of the absorptive characteristics of different sampleconstituents and different adsorbent material may be used to advantagein several ways. More particularly, the two active cells S, and S can befilled with different types of adsorbent, as previously referred toabove. It would be fortuitous that two different adsorbent materialswould give the same relative response for chemically differentcompounds. Comparison of the output signals E, and E from the two cellsS, and S provides qualitative information on the chemical identity ofthe sample material. Furthermore, one particular adsorbent may give abetter response for many of the compounds in a sample, while anotheradsorbent gives a better response for the remaining compounds. Aninvestigator, offered the additional degree of freedom of the secondadsorbent, should be able to optimize his system for maximum response.

Moreover, overlapping microadsorption detector peaks may be difficult toquantitate. By the use of selective adsorbent materials in cells 8, and8,, such adsorbents having characteristics which complement each other,it is possible to achieve a greater separation between peaks. In anideal case, alternative peaks would occur on each of the twochromatograms as schematically indicated by the signal traces in FIG. 5.

One additional use for the adsorption detector employing two samplecells S, and S is for measuring relative strengths of adsorption ofdifferent sample-solvent-adsorbent combinations under conditions closelyapproximating the chromatographic column. Thus, valuable informationregarding suitable combinations for packing various chromatographiccolumns may be obtained. The strength of adsorption of a column packingmaterial in one cell S, is comparable directly to a standard adsorbentin the other cell S Or the relative strengths of adsorption for twomaterials of interest are comparable directly.

Referring now to FIG. 6, there is shown an alternative adsorptiondetector 25 incorporating features of the present invention. Detector 25is identical to detector 1 of FIG. 1 with the exception that anadditional reference cell R, has been added serially in the flow pathwith the other cells 5,, R, and S Detector 25 would be used in a bridgenetwork of the type shown in FIG. 7. The bridge network of FIG. 7 issubstantially the same as that previously described with regard to FIG.3 with the exception that the second reference cell R is placed in thesecond bridge l6 and the first reference cell R, is placed in arm 11 ofthe first bridge. The switching arrangement for switching the referencesample between the two bridges is thereby eliminated. The secondreference cell R may be packed with an inert or relatively inactiveadsorbent fill material, such as glass beads, or it may be left empty.The two bridges 12 and 16 are balanced for the pairs of sensing andreference cells S, and R, and cells S and R respectively, in the absenceof a sample constituent to be detected.

In operation, heat exchange of the sample constituents on the adsorbentin the sensing cells S, and S produces output signals E, and Erespectively, which may then be compared in the comparators of FIGS. 4or 5, as desired. The detector 25, bridge circuit of FIG. 7 and thecomparators of FIGS. 4 and 5 may be used in precisely the same manner aspreviously described with regard to the three-cell detector 1. Theadvantage of the four-cell detector 25 is that the switching andsynchronous detection features may be eliminated by the mere addition ofone additional reference cell R Referring now to FIG. 8, there is showna plot of recorder chart scale deflection, A, versus flow rate in ccsper hour of the flow stream for two conditions of bridge voltage and twoconditions for the pairs of detector cells (S-R pairs), namely, packedor empty. The curves of FIG. 8 indicate the fluctuations in backgroundsignal as a function of the flow rate. Thus, it is seen that a pulsatingflow stream, such as that obtained by use of a pulsating pump, wouldintroduce serious noise in the output signal. Therefore, it is desiredto obtain means for compensating for the dependence of the output signalupon the flow rate of the stream to be detected. An interestingcharacteristic of the curves of FIG. 8 is that the flow rate dependenceof the output signal from a pair of packed cells, i.e., ones packed withadsorbent or with an inert material, is substantially the same as thatfrom a pair of empty cells. Furthermore, it is seen that by changing thebridge voltage the two curves can be brought into coincidence.

Referring now to FIG. 9, there is shown a bridge network 26 forcompensating for changes in the output signal due to changes in the flowrate. More particularly, the bridge network 26 of FIG. 9 issubstantially identical to that previously described with regard to FIG.7 except that the second sensing or sample cell S, in bridge 16 has beenreplaced by reference cell R, which may be either an unpacked sensingcell S or such a sensing cell 8; packed with an inert packing material.In addition, a pair of variable resistors 27 and 28 have been providedfor adjusting the voltages applied to the bridges l2 and 16,respectively.

The two output signals E, and E, from the bridge 26 are fed to acomparator or subtractor circuit 29, as shown in FIG. 10. In thesubtractor circuit, the two input signals E, and E are subtracted toobtain the output signal E, which is thereby cor rected for flow ratefluctuations. If necessary, resistors 27 and 28 are adjusted to bringthe flow rate characteristic curves into coincidence, as previouslydescribed with regard to FIG. 8. In this manner, the output signal E issubstantially completely corrected for flow rate fluctuations and thispermits a pulsating type pump to be utilized for producing the flow inthe sample stream 2.

Referring now to FIG. 11, there is shown an alternative bridge network3! to that previously described with regard to FIGS. 9 and 10. In thisembodiment, the reference cells R, and R are placed in the two arms ofthe bridge on the opposite side of the bridge from arms 9 and 11 whichcontain the detector cells S, and R,. The output signal E is therebycompensated for fluctuations in flow rate and the only signal appearingat the output E, would be due to the heat exchange conditions occurringwithin the sensing or sample cell, 8,.

In all of the above bridge circuits, individual output signals from eachof the cells are combined in pairs to form at least two separatecomposite output signals. For example, the output signal from the firstsensing cell S, is combined with the output signal of the reference cellR, to produce a composite signal in the diagonal of the bridge which isrelatively insensitive to changes in the ambient temperature, sinceambient changes would influence both detectors in a like way. in otherwords, the combined output signal changes only when the thermalconditions in one of the cells changes relative to the thermalconditions in the other cell. Likewise, the second detector cell 5, hasits output combined with the output signal from the reference cell R,or, in the case of the four-cell detector, with the second reference R,to produce a second composite signal in the diagonal arm of the bridge.These two composite output signals may then be compared, as by acomparator which gives only the difference between the two or bysimultaneously recording the two composite signals for visualcomparison, as shown in FIG. 5.

Referring now to FIG. 12, there is shown, in longitudinal section, afour-cell microadsorption detector of the type schematically indicatedin FIG. 6. The detector includes a pair of stainless steel disc-shapedflanges having a central bore 36 therein to define a portion of the flowpassageway for flow of the fluid stream 2 through the detector 25. Aplurality of Teflondiscs 37 are centrally apertured at 38 and axiallystacked in the space intermediate the flanges 35 to define the main bodyof the detector 25. The thermistors 7 are centrally mounted in each ofthe discs 37 with the thermistor element projecting into the flow stream2. The filter membranes 6 separate the discs 37 to define the boundariesof each of the detector cells. Suitable packing material is placedwithin the cells defined by the spaces between the filter membranes 6. Ametallic center disc 41 as of stainless steel is placed midway in thestack of the Teflon discs 37 for separating the upstream two detectordiscs 37 from the downstream two detector discs 37. The central passagein the center disc is constricted rela tive to the passageways throughthe Teflon discs 37 such that heat evolved into the flow stream 2 by thethermistor detectors in the upstream portion of the detector is absorbedby the center disc to render the downstream detectors relativelyinsensitive to flow rate conditions produced by the upstream detectors.This feature of the metallic heat absorbing disc between a pair ofmicroadsorption cells forms the subject matter of and is claimed in U.S.Pat. No. 3,535,918 issued Oct. 27, 1970 and assigned to the sameassignee as the present invention. Since many changes could be made inthe above construction and many apparently widely different embodimentsof this invention could be made without departing from the scopethereof, it is intended that all matter contained in the abovedescription or shown in the accompanying drawings shall be interpretedas illustrative and not in a limiting sense.

What I claim is:

1. In a microadsorption detector, means forming a plurality ofadsorption detector cells serially disposed in close proximity to eachother along the flowpath for a fluid stream to be deteeted, each of saidcells including a thermally responsive sensing element for deriving anoutput determinative of the adsorption in the respective cell of certainconstituents of the fluid stream, THE IMPROVEMENT WHEREIN, at least oneof said cells including active adsorptive packing material and theremainder of said cells having relatively inactive packing material,there are at least three of said serially disposed adsorption detectioncells, means combining the individual outputs of each of said cells inpairs to form at least two separate composite output signals, suchcomposite signals each'comprising a combination of the outputs of atleast two cells and means comparing the composite output signals.

2. The apparatus of claim I wherein said plurality of serially disposedadsorption cells comprises at least four of said adsorption cells.

3. The apparatus of claim 1 wherein at least two of said cells includesa relative active adsorptive packing material for a constituent of thefluid stream as compared to the adsorptive characteristics of thepacking material, if any, of said third cell.

4. The apparatus of claim 1 wherein said comparing means includes arecorder for recording the separate composite signals for comparison.

5. The apparatus of claim 1 wherein said combining means includes a pairof wheatstone bridge networks, and wherein said comparing means comparesthe separate outputs of said pair of wheatstone bridge networks.

6. The apparatus of claim 2 wherein at least three of said detectioncells each includes a relatively inert adsorptive fill material, if any,as compared to a relatively active fill material disposed within saidfourth cell, means for combining the outputs of two pair of said cellsto produce a pair of composite outputs, and means for comparing thecomposite outputs to derive an output which is relatively independent ofthe rate of flow of said stream.

7. The apparatus of claim 1 including a liquid chromatographic columndisposed upstream of said detector cells such that said detector cellsare disposed to detect the effluent liquid stream of said column.

1. In a microadsorption detector, means forming a plurality ofadsorption detector cells serially disposed in close proximity to eachother along the flowpath for a fluid stream to be detected, each of saidcells including a thermally responsive sensing element for deriving anoutput determinative of the adsorption in the respective cell of certainconstituents of the fluid stream, THE IMPROVEMENT WHEREIN, at least oneof said cells including active adsorptive packing material and theremainder of said cells having relatively inactive packing material,there are at least three of said serially disposed adsorption detectioncells, means combining the individual outputs of each of said cells inpairs to form at least two separate composite output signals, suchcomposite signals each comprising a combination of the outputs of atleast two cells and means comparing the composite output signals.
 2. Theapparatus of claim 1 wherein said plurality of serially disposedadsorption cells comprises at least four of said adsorption cells. 3.The apparatus of claim 1 wherein at least two of said cells includes arelative active adsorptive packing material for a constituent of thefluid stream as compared to the adsorptive characteristics of thepacking material, if any, of said third cell.
 4. The apparatus of claim1 wherein said comparing means includes a recorder for recording theseparate composite signals for comparison.
 5. The apparatus of claim 1wherein said combining means includes a pair of wheatstone bridgenetworks, and wherein said comparing means compares the separate outputsof said pair of wheatstone bridge networks.
 6. The apparatus of claim 2wherein at least three of said detection cells each includes arelatively inert adsorptive fill material, if any, as compared to arelatively active fill material disposed within said fourth cell, meansfor combining the outputs of two pair of said cells to produce a pair ofcomposite outputs, and means for comparing the composite outputs toderive an output which is relatively independent of the rate of flow ofsaid stream.
 7. The apparatus of claim 1 including a liquidchromatographic column disposed upstream of said detector cells suchthat said detector cells are disposed to detect the effluent liquidstream of said column.